作者
Alice T Shaw, Dong-Wan Kim, Ranee Mehra, Daniel SW Tan, Enriqueta Felip, Laura QM Chow, D Ross Camidge, Johan Vansteenkiste, Sunil Sharma, Tommaso De Pas, Gregory J Riely, Benjamin J Solomon, Juergen Wolf, Michael Thomas, Martin Schuler, Geoffrey Liu, Armando Santoro, Yvonne Y Lau, Meredith Goldwasser, Anthony L Boral, Jeffrey A Engelman
发表日期
2014/3/27
期刊
New England Journal of Medicine
卷号
370
期号
13
页码范围
1189-1197
出版商
Massachusetts Medical Society
简介
Background
Non–small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase gene (ALK) rearrangement is sensitive to the ALK inhibitor crizotinib, but resistance invariably develops. Ceritinib (LDK378) is a new ALK inhibitor that has shown greater antitumor potency than crizotinib in preclinical studies.
Methods
In this phase 1 study, we administered oral ceritinib in doses of 50 to 750 mg once daily to patients with advanced cancers harboring genetic alterations in ALK. In an expansion phase of the study, patients received the maximum tolerated dose. Patients were assessed to determine the safety, pharmacokinetic properties, and antitumor activity of ceritinib. Tumor biopsies were performed before ceritinib treatment to identify resistance mutations in ALK in a group of patients with NSCLC who had had disease progression during treatment with crizotinib.
Results
A total of 59 patients were …
学术搜索中的文章
AT Shaw, DW Kim, R Mehra, DSW Tan, E Felip… - New England Journal of Medicine, 2014